Use and Prescription of Direct Oral Anticoagulants in Older and Frail Patients with Atrial Fibrillation: A Multidisciplinary Consensus Document.

In the last twelve years the clinical management of patients with atrial fibrillation has been revolutionised by the introduction of direct oral anticoagulants. Despite the large amount of evidence produced, some populations remain relatively poorly explored regarding the effectiveness and safety of direct oral anticoagulants, such as the oldest and/or frailest individuals. Frailty is clinical syndrome characterized by a reduction of functions and physiological reserves which results in individuals having higher vulnerability. While current evidence underlines a relationship between atrial fibrillation and frailty, particularly in determining a higher risk of adverse outcomes, data regarding effectiveness and safety of direct oral anticoagulants in frailty atrial fibrillation patients are still lacking, leaving uncertainty about how to guide prescription in this specific subgroup. On these premises, this multidisciplinary consensus document explains why it would be useful to integrate the clinical evaluation performed through comprehensive geriatric assessment to gather further elements to guide prescription of direct oral anticoagulants in such a high-risk group of patients.

How and when to measure anticoagulant effects of direct oral anticoagulants? Practical issues.

Direct oral anticoagulants (DOACs) do not require dose adjustment based on laboratory testing. However, it might be necessary to measure their plasma concentrations in the following specific situations: 1) before thrombolytic therapy in patients with stroke; 2) before surgery or invasive procedure; 3) in case of adverse events (thrombosis or hemorrhage); 4) when immediate reversal of anticoagulation is needed; 5) in patients with extreme body weight; 6) when administering additional drugs potentially interfering with DOACs; and 7) when overdosage is suspected regardless of concomitant bleeding. Basic coagulation tests, such as prothrombin and activated partial thromboplastin time, should not be used as standalone tests to assess the levels of anticoagulation as they are not specific for DOACs and their results are dependent on the type of reagent used for testing. Plasma DOAC concentrations should be assessed by dedicated tests: dilute thrombin time or ecarin tests (for dabigatran) or anti-factor Xa assays (for anti-factor Xa inhibitors). Dedicated tests should be calibrated against their respective plasma calibrators at certified DOAC concentrations and results should be expressed as ng/ml. Caution should be exerted when interpreting the results of the most common hemostatic parameters such as antithrombin, proteins C and S, lupus anticoagulant, or individual coagulation factors, as they may be strongly affected by the presence of a DOAC. Whenever possible, these parameters should be measured 4 to 5 days after discontinuation of DOAC anticoagulation.